Increased production of IL-6 and IL-17 in lipopolysaccharide-stimulated peripheral mononuclears from patients with rheumatoid arthritis

Abstract

TLR4-mediated inflammatory responses are important for innate immune functions, thus their alterations may participate in the pathogenesis of rheumatoid arthritis (RA). Cortisol is one of the most potent immunomodulatory hormones involved in control of inflammation. In this study, we analyzed TLR4-mediated responses and cortisol effects on the process in peripheral blood mononuclear cells (PBMC) from RA patients. Lipopolysaccharide-stimulated PBMC from 23 female patients and 15 healthy controls were cultured in the presence or absence of cortisol (1 μM) for 24 h. A panel of 17 inflammatory cytokines was analyzed in the cell culture supernatants. Higher (p < 0.05) concentrations of IL-6, IL-17 and MCP-1 were found in lipopolysaccharide-stimulated PBMC from RA patients compared to controls. After normalization of stimulated cytokine secretion to unstimulated cells, a significantly higher (p < 0.05) IL-6 and G-CSF production was found in RA PBMC. Cortisol induced stronger (p < 0.05) suppression of lipopolysaccharide-stimulated secretion of IL-1β, IL-6, IL-17 and G-CSF in RA group compared to controls. The observed higher production of the key inflammatory cytokines by RA PBMC to lipopolysaccharide stimulation supports involvement of TLR4-mediated processes in RA pathogenesis. The higher sensitivity of LPS-stimulated RA PBMC to immunosuppressive effects of cortisol may reflect adaptive processes to chronic inflammation.

Grape seed proanthocyanidin extract ameliorates murine autoimmune arthritis through regulation of TLR4/MyD88/NF-κB signaling pathway

“…LPS-induced TLR4 activation was greatly enhanced in peripheral blood mononuclear cells (PBMCs) from patients with RA than in those from patients with OA or healthy controls [ 30 ]. TLR4 activation by LPS induces the production of pro-inflammatory cytokines in human FLS and PBMCs from patients with RA [ 31 , 32 ]. TLR4 upregulation increases pro-inflammatory activity and induces degeneration in chondrocytes [ 33 ].…”

Modulators affecting the immune dialogue between human immune and colon cancer cells

“…The ability of PBMC to produce inflammatory cytokines plays a major role in the modulation of chronic inflammatory responses associated with carcinogenesis. This particular function is promoted by various factors, such as amorphous silica particles capable to increase IL-1β and IL-8 production [25] , and cortisol that have been shown to suppress secretion of IL-1β, IL-6, IL-17 and G-CSF [26] . Recently, Veinalde et al [27] have reported that double stranded RNA has the capacity to induce PBMC to produce a considerable number of both pro-and antiinflammatory cytokines.…”

The association of toll-like receptor 4 gene polymorphisms with primary open angle glaucoma susceptibility: a meta-analysis

“…For instance, TLR4 knockout mice reduce autoantibody production and vasculature inflammation in systemic lupus erythematosus (SLE) and atherosclerosis, respectively [44,45]. The activated TLR4 by using endogenous ligands induces pro-inflammatory cytokine and chemokine production in both human synovial fibroblasts and peripheral blood mononuclear cells (PBMC) from rheumatoid arthritis patients leading to cartilage inflammation and degeneration [46][47][48]. In multiple sclerosis patients and experimental autoimmune encephalomyelitis models, the TLR4 was up-regulated and HMGB-1, a TLR4 ligand, plays a role in the disease progression [49][50][51].…”